Will a patient with ulcerative colitis (UC) and a flare of colitis benefit from antiviral therapy for concomitant Cytomegalovirus (CMV) colitis?

From the Guidelines

Yes, there is evidence that patients with ulcerative colitis who have concurrent CMV colitis may benefit from antiviral therapy. The most recent and highest quality study, 1, recommends treatment with intravenous ganciclovir 5 mg/kg twice daily for 5–10 days, followed by oral valganciclovir 900 mg daily until completion of a 2–3 week course. This approach is supported by other studies, including 1 and 1, which suggest that antiviral therapy can improve outcomes in patients with moderate to severe colitis who are steroid-refractory or steroid-dependent. The decision to treat CMV colitis in ulcerative colitis patients should be based on the severity of the colitis and the extent of CMV involvement, as well as consideration of the potential risks and benefits of antiviral therapy. Some key points to consider when treating CMV colitis in ulcerative colitis patients include:

• The importance of early diagnosis and treatment, as prompt antiviral treatment and temporary discontinuation of immunomodulators can be associated with clinical improvement and decreased mortality, as noted in 1.
• The need for careful monitoring of renal function and bivalent electrolytes, as well as the potential for significant irritation and ulceration in the genital area, as noted in 1.
• The potential for antiviral therapy to allow better control of the underlying inflammatory bowel disease and improve response to immunosuppressive therapy, as suggested in 1. Overall, the evidence suggests that antiviral therapy can be a valuable treatment option for patients with ulcerative colitis and concurrent CMV colitis, particularly those with moderate to severe disease who are steroid-refractory or steroid-dependent.

From the FDA Drug Label

The incidence of CMV disease at 6 months is summarized in the table below: Incidence of CMV Disease at 6 Months (Kaplan-Meier Estimates) CMV Disease at 6 months Ganciclovir (n = 150) Placebo (n = 154) Relative Risk (95% Cl) CMV Disease,* N (%) 7 (4.8%) 29 (18.9%) 0.22 (0.10,0.51) CMV syndrome# 6 (4.1%) 19 (12.4%) CMV hepatitis 1 (0.7%) 9 (5.9%) CMV GI disease 0 (0%) 3 (2%) CMV lung disease 0 (0%) 4 (2. 6%)

There is no direct evidence in the provided drug label that supports the use of antiviral therapy for CMV colitis in a patient with ulcerative colitis. The label discusses the prevention of CMV disease in subjects with AIDS and transplant recipients, but does not address the treatment of CMV colitis specifically 2.

From the Research

CMV Colitis and Ulcerative Colitis

• The presence of CMV colitis in patients with ulcerative colitis (UC) can lead to worse outcomes, including increased colectomy rates 3, 4.
• CMV reactivation is common in patients with severe UC and may reflect exacerbation of mucosal inflammation and/or administration of immunosuppressants 5.
• The detection of CMV in the setting of UC often creates confusion about whether CMV is a 'bystander' or 'disease' 4.

Diagnosis of CMV Colitis

• The diagnosis of CMV colitis rests on the presence and abundance of viral inclusion bodies on hematoxylin and eosin stain, positive immunohistochemistry, and/or positive tissue polymerase chain reaction 4.
• Quantitative tools, such as the number of infected cells or copies of the genome, are important in determining the density of infection 6.

Treatment of CMV Colitis

• Antiviral therapy, such as ganciclovir, is recommended for patients with high-grade CMV infection or severe disease 6, 4, 5.
• The timing and duration of antiviral drugs in CMV disease is debatable, but depends on the load of CMV in tissue 4.
• Tumor necrosis factor inhibitors may be useful for treating underlying disease activity in the setting of CMV colitis 4, 5.
• High-dose valganciclovir may be a treatment option for CMV colitis with ganciclovir resistance due to dual UL97 and UL54 gene mutations 7.

Benefits of Antiviral Therapy

• Antiviral therapy can significantly reduce the need for colectomy in patients with severe UC and high-grade CMV infection 5.
• Controlling systemic inflammation and reducing complications is crucial in the short-term therapy for UC patients with CMV colitis 3.
• Antiviral therapy may also help in reducing the risk of early relapse in UC patients with CMV colitis 3.